Hi, everyone, and welcome. My name is Veronica Feinberg, and I'll serve as your moderator today. Thank you for joining us for today's webinar. Collaborative bioprocessing Next Gen. Mab Downstream manufacturing Enhanced by Transcendental Partnership. As your moderator, it's my role to ensure that we make the most of your time with us. I'm here today with Doctor Paul Beckett, Kara Pizzelli, Jerome Dillon, Chris Huang, and Jewel Zhu. Paul holds a bachelor's degree in biochemistry from Imperial College London and has a master's degree and doctorate in biochemical engineering from University College London. Paul has worked in the Pharmaceutical industry for 20 years and has held a number of roles in this capacity, including managing bioprocesses for early phase clinical material, CMC regulatory affairs, consultancy, and program management of the Next Generation Bioprocessing Initiative. His current role is the Global GTM lead for the chromatography and clarification technologies at our company. Kara Pizzelli holds an Ms. degree in Chemical Engineering. Her career started at our company 25 years ago, focusing on the optimization and scale up of the unit operations from clarification to bulk drug drug filtration for customers in the US. Kara more recently managed the global clarification business, owning the strategy and innovation before taking on the role of DSP Downstream Strategic Product Manager in the Bio Continuum business franchise in 2023. Jerome Dallin holds an Ms. engineering degree in Industrial manufacturing and biological engineering. He began his career at Snow Free Pasture 21 years ago, focusing on vaccine process development in France, Canada and USA. In 2013, Jerome joined our company to manage bioprocessing sales and later transitioned to the strategy organization to lead global initiatives for vaccines and the factory of the future. In his current role, Jerome is at the helm of Alliance Management, driving the development of the Biocontinuum platform across the biopharmaceutical industry. Chris Huang holds a pH D in Biochemical Engineering from MIT and has over 30 years of experience in the biopharmaceutical industry. He began his career at Genzyme and later at Snow Fee, supporting and leading CMC development as well as process and technology development. He also served as project lead for the Integrated Continuous Biomanufacturing Platform program. Chris joined HJB Transcenta in 2016 where he's responsible for CMC development and developing and industrializing highly intensified biomanufacturing platforms to increase facility output, enhance process control, and reduce the cost of goods to expand patient access to innovative biologics. Jules Zoo holds an Ms. Engineer degree in biology and bioprocessing engineering. He joined the HJB company in 2018 as a scientist to develop downstream purification process for CMC. Since 2020, he joined the HJBHICB group and started to build and support continuous purification platform for advanced antibody manufacturing. In his current role, Juul is working on HICB transcendence, platform development, and supporting continuous manufacturing control strategy. So before I turn things over to our presenters, I'd like to cover a few housekeeping items. At the bottom of your screen are multiple application widgets that you can use. There you can also find our reaction button, indicated by the thumbs up emoji that allows you to give immediate feedback on the presentations, topics, or anything that stands out. All the widgets are sizable and movable, so feel free to move them around. To get the most out of your desktop space, you can expand your slide area or maximize it to full screen by clicking on the arrows in the top right corner. 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And so that's it from my side and it's my pleasure now to turn things over to our speakers. Thank you, Veronica, and hello, everyone. I'm Jerome Dalla and I'm excited to start today's presentation on collaborative frontiers in bioprocessing, next generation monoclonal antibody downstream manufacturing with our partner Transcenta. Let's take a quick look at our agenda for today. We will begin with the details of our collaboration, followed by an introduction to our Bio Continuum platform. We will next explore Transcenta and their process ideology. We'll then dive into specific topics such as bio, such as continuous downstream design survey, bio burden management and GMP implementation case study. Finally, we will wrap up with a QNI session. To begin, here are the details of our collaboration with Transcenta. And let's first dive into why our collaboration with Transcenta is so crucial and the significant milestones we have reached. Our collaboration strategy is centered on partnering to enhance and rapidly adapt by a continuum platform technologies. This partnership is designed to leverage and combine strengths and accelerate the adoption of our of innovative solutions. Our focus areas include early product development process, improving connectivity and tackling in house challenging projects. These areas are critical for advancing our capabilities and delivering effective solutions to the market. Regarding our partner profile, we part we prioritize initiatives that are funded, have strong adoption drivers and are open to Co publish and promoting our advancements. This alignment ensures both parties are fully committed to the success of this project. Our technology focus encompasses several key areas flow through polishing and multi column chromatography. This collaboration is poised to lead us in developing robust, ready to use a ready implementation solution. Sorry. Now let's look at our four year journey of innovation and collaboration. Here's a timeline highlighting, highlighting our quick milestones and achievement from 2019 to 2023. In September 2019, we started our partnership discussions with Transanza and the following year in June, we officially announced our collaboration aimed at developing a comprehensive downstream process with the finalization of the design in November. In January 2022, we successfully delivered the flow through polishing system to Transcenter and 10 months later in October, Transcenter integrated our single use Mobius multi column capture system. And finally in 2023, Transcenter achieved the first GMP production batch. Its progress highlights our dedicated efforts and successful collaboration strategy. Now let's transition to our next topic, which is the introduction to our Bio Continuum platform. For this, I will hand over to my colleague Kara. Thank you, Jerome. This slide shows the trends and drivers behind the progression to intensified processing. Our Bio Continuum platform aligns with the Bio Forum operations group drivers and their technology road map. In today's environment, we're familiar with individual unit operations and their aisles of automation. Biocontinuum platform supports moving to digitally connected operations and lights out manufacturing in the facility of the future. This facility of the future is not so much a destination, but a concept where we need to define new technologies and implement these technologies to bring this vision to reality. In Biocontinuum, these technologies are grouped into four distinct but complementary areas. Technologies that enable process intensification, those supporting automation and integrated process control, process analytical technologies and capabilities supporting improved knowledge management and data analytics. The Biocontinuum platform builds on our core expertise and mutually exclusive unit operations of batch and fed batch processes. And these four focus areas will converge to enable intensified and continuous bioprocessing, which brings us to this slide showing the traditional approach for harvest and purification compared to a new process. In today's processing of a batch of fed batch, bioreactor operators are running through upstream clarification and downstream purification by way of centrifugation and or depth filtration, affinity chromatography, viral inactivation, neutralization, ion exchange chromatography, virus filtration and final UFDF and isolated connected and isolated disconnected unit operations. The process of the future utilizes technologies connected and controlled together to enable intensified and continuous operation. Now from a cell retention device through continuous capture directly through viral and activation neutralization and again directly through flow through polishing and and further downstream. Incorporating flexibility and modularity is also very important so that the user may set their process for a hybrid operation or a fully continuous or for different molecules. And then this brings us to the next section where I will now hand off to Chris for an introduction to Transenta and their process ideology. Thanks, Carol. Thanks for having me here. So let me briefly introduce our company and take this opportunity to highlight reasons why we decided to innovate how we manufacture our trophy drugs. Transenta is a clinical stage by our pharma company with full capability from discovery to manufacturing targeting various disease areas. Currently, our lead asset Osimitimat has shown some very promising clinical data and for treating gastric cancer patients and is now entering the final stages of clinical development for today's presentation on this new platform. The work was carried out by our very capable team at HJB, which is a subsidiary of Transcenta responsible for CMC development manufacturing in support of pipeline as well as our CDMO partners. In terms of why we decided to develop this platform, when I first joined a company back in 2016, we knew that in order for us to be a successful company, not only do we need to develop safe, efficacious and I'll say differentiated drugs, but our process intensification is absolutely critical because we face, I would say, two key challenges. One is really around the increase of drug pricing pressure once around drug pricing pressure that especially in the areas of emerging markets such as China where the drug prices can drop as much as 50 to 90% when you when the drugs are imported from the US. And of course we also have a competition from other novel drugs and biosimilars and new modalities such as gene cell and gene therapy. The other challenges that we decided very early on to develop our own CMC capability and build our own manufacturing facilities. So we also faced a challenge of expensive high facility cost and also the risks associated in terms of demand uncertainties. So we needed to innovate to significantly lower the cost, facility cost and also the cost of goods where the cost of goods is not simply just a competitive advantage, but in many cases a necessity. We also need to designer facilities such that we can very much simplify so that we can provide the speed and the capacity and also increase our response time to change in demands. And lastly, continue to increase the process robustness and then decrease operational risk to ensure supply to our patients. And by achieving these objectives, by achieving these objectives, we will address some very important business and societal needs, ensuring that the requirements of the business, the patients and the Society of fully aligned. So what we envisioned back in 2016 when I first joined the company is that our processes needs to be very, very productive and also we need to really decrease the cycle time to minimize down time. So together by doing that, we can really maximize our facility output. And because a process of very productive, we can expand by simply scaling up with identical trains that we can wheel into our facility and while minimizing the comparability risk on the on the facility standpoint, it needs to be single use, it needs to be very simple and that allow us to lower the cost of facility, but also for a relatively small footprint to really increase our response time. So since we think the and that that allow us to again having a small, really small facility to provide the output of much larger facilities. So since continuous process is able to meet all these process requirements. Now we made a constant decision in the very beginning to leverage our team's experience and expertise to develop this high CD platform. It stands for highly intensified continuous bioprocess platform for our facility. So our, our approach is to maximize output. So you can maximize output while decreasing of course the CapEx and OpEx to so we can significantly lower the cost of goods. And by focusing on maximizing the self culture up through continuous perfusion, which in my opinion has the greatest potential for maximizing productivity. And then you're integrated with a highly intensified downstream to Debon and like your output of course with the appropriate media concentrates and buffer prep solutions to really maximize the space times in Geo the facility output. So we started this five year journey when our facility was first opened back in 2018. First we focus on the continuous perfusion because we need to have this process rated by middle of 2023 to support our our late stage production. So we focus on the perfusion side by developing this platform, developing our own perfusion media. And then within the first couple years we were successfully developed what we call this plug and play platform as well as push the high to significantly increase the property where we were seeing 10 to more than 15 times increase in productivity when comparing to the same cell line of in the Fed batch for multiple cell lines and molecules. In fact, last year we achieved 8 grand square per day which correspond to more than 700 kilograms of drug sensors per year for a single 500 liter single use bioreactor. We saw. We also seen a much improved product quality in terms of aggregation man 5 charge variant profiles and also this platform can also produce less less stable protein as well. On the downstream side, we decided to collaborate with Jerome and Cara and their team to Co develop this automated single use floating policy system back in the middle of 2020 and then to leverage their continuous capture system to intensify our downstream. And I'm very happy to say that as of last year we were very successful in in this first time success in doing GMP manufacturing usage platform to support our late stage programs. So when you put it all this together, you know, we believe the high CP can provide the economy of scale from much smaller and more flexible and cost effect facilities. And this comparison basing on experience in building our facility and running our facility highlights the benefit of high CP where we compare 2 facilities using the same cell line and same and same and, and matching the output 4 by 1000 meter bio reactors can produce as much as 20, two 2000 meter fit batch bio reactors. You can see a significant decrease in number of runs per year. The facility cost is significantly lower and the manufacturing headcount is also significantly lower as well. And then using our own internal cost of goods model, using actual cost, we were projecting more than 50% decrease in the cost. So you can see that there's a dramatic benefit of using this platform and then give you a sense of the the benefit here is that for two ton facility output we can save more than $100 million of saving and that money can be piled invested back into our R&D. So I hope you've shown that by applying the high CD platform, which is an even lower the cost increases speed, flexibility and quality to support our business and also for our patients. So with that in mind, I'm going to turn off the jewel who will talk about our design philosophy and our hyper continued downstream and also our exciting progress to date. Well. Thanks, Chris. I'm Joel. And now let me further explain the consideration and the design of our HJP continuous downstream platform. There are two voice talking out loud to transfer from conventional batch production to a continuous production. One is the end to end process from affinity capture to TFF. In this mode, products from one operation unit can be directly processed by the next unit to achieve fully continuous. The 2nd is the hybrid continuous process. The professional cell culture and capture are performed continuously and the subsequent polishing steps are also performed continuously. It is a simplified same continuous process. So what our HJB choose to answer this question and let's think about our goals again, As just Chris said, our HJB aim to the bottleneck while integrate and automated continuous downstream process to mix my site space-time yield and the facility output. So to achieve this, there are several key objectives for continuous and maybe Chris have highlighted again. And 1st, it can support multiple products and multiple director. It is promised to be single use, could minimize footprint and with a high output for all unit operation, it can fast cycle time, minimize downtime. There is a need for each of the operation. Robust performance and a good value version control. Of course, it should be easy to transfer and develop reducing difference from batch process to minimize the comparability risk and we hope it could be ready by mid 2023. So HJV choose to integrate hybrid continuous process by focusing on connecting and automating exist batch operations becoming the current high CB platform. So here I would present the process and the technology that HJB adopt to achieve the continuous platform described above. The. 1st is the capture part which enables continuous combatography. We use the multi column capture system, the MCC for uninterrupted load with three columns. The continuous capture can triple the output compared to the batch operation. This approach also saves hold tanks, mixing bags and affinity batch. In addition, it enhance the affinity resin utilization catching the upfront resin cost by 60% that will perform very inactivation. It can perform the either by a continuous VI connected to the capture or in a batch VI. Then it comes to the continuous polishing. It is important to emphasize the connected automated flows through polishing system. FTP it was called developed by HJB and the Jerome Karas team. This system integrates up to four flows through process in one control system. By using FTP we can free up a pre viral downstream capacity by more than 40% and increase output from more than 10 times compared to manual batch operation. FTP system can automate all polishing steps within two days after initial setup and the no extra in process hold tanks are required. The platform also reduced upfront polishing resin by 60% that the polishing after the position step, the bug batch UFDF and the bug fail is followed. This entire hybrid continuous downstream platform have fully GMP operational since middle 2023. So after reviewing the whole platform, we can better understand why we don't choose an end to end process. The main drawback of the fully continuous is that the throughput is limited by profession rate and the entire purification line is occupied means 6 downstream prints are required for six bioreactor. In contrast, the hybrid continuous process can support the six bioreactor with only one, the reduced line save buffer tanks and the purification suits, which means save money and space. It also reduced the reliance on complex design of hardware and the decreased operation risk. It is more flexible and handle to handle excursion more compatible with different upstream titles and the downstream process scenarios. Now let's back to the continuous technology we have. We achieved uninterrupted sample loading at a diff at the capture and the polishing stage. The automatic switching is controlled by loaded density of chromatography and filtration entered in the MCC or FTP. One branch is keep loading when the others are running in the rest functions like equilibration, wash, illusion and strip. The principle is same for two branch design and three branch designs. However, this technology is primarily based on inline UV flow totalizer and the pressure indicator. No new sensors are implemented, so it is still easy to set up and robust in performance. If it is not complicated for continuous loading, there are many. Factors to consider in developing and designing for the continuous process, the first consideration is the search tank. Search Tank We minimize the size of Search tank to reduce product dispersion and enhance the product contrib ability and the traceability. But the surge vessel should be still big enough to match the process mass flow and not affect the subsequent operations in case it is sensitive to feed the changes. Therefore lot of traceability and the deviation management, it is important to characterize the resistant time distribution through the process by building RTD model. Good risk analysis like a filtration and the column following can help predict deviation and carry out preventive actions. PIT is used is a good tool to real time monitoring of system performance including protein concentration and aggregation. Scale up and scale down. Also the challenges in continuous. We made it customize Octa and the pumps to build a appropriate scale down model. The hybrid continuous process also simplify the process development and the characterization because it is less different from a batch process. Finally, the cost of goods we designed to increase throughput and decrease equipment and a single use compounds cost. In practice. I'd like to discuss on MCC and the FTP in detail. First is MCC. The MCC system was put in the same room and next to the perforation bioreactor you can see in the picture and their burden control needs to be considered first. For MCC, things like a compound connection, sanitization procedures, sampling strategy are all important we will discuss later. And for loading strategy, naughty column capture are always advertised in overloading to maximize resin utilization. However, it is highly dependent on the title from profession. So we would like to run in a non overload mode. This can fast cycle time, ease the process development process, scale down and the future VC study. Well, it doesn't have too much difference in resin cost. Then for creation in title and residence, time should be characterized and the lifetime of compounds and the prop drafting should be verified. FTP is more complex because it integrates 4 steps from depth filtration to various filtration. We already talked about the branch switching by protein or volume totalizer and it is also able to adjust the pH and the conductivity automatically in search tanks before going to the next unit as a flow through polishing system. The FTP also supports chromatography to operate in binded loot mode for better impurity. Remove. But a flow through chromatography is more suitable for flow rate control and better resin utilization. We should take this into consider during process development before it comes to continues. As for various filtration, we compare the constant flux versus constant pressure from the continuous point of view. We choose the constant flux for easy operation and stable running, but notice this will also influence the strategy on BC study. Similar we should know. The frustration range in concentration and flow rate. Similar, we should know the tank level should be targeted and well controlled by fluoride management. Again, the system compounds are always the concerns. So above are the designs and the considerations of our continuous platform focus on MCC and FTP system. Then I want to share the most important part. When scale up the continuous process, the better burden management compared to a batch processing. The whole process lasts only a few days from harvest to Buckfield and the pores are filtered between unit operations. But there's a continuous process required a long time running and the steps connected to each other. The filters are only settled for particular remove which is significantly increased the bail burden risk during long term operation. So to get this over, we consulted a lot of literature and draw on the experience of leading companies. Then summarize a bail burden control strategy based on three points, prevention, removal and detection, which are highlighted in Nmap. First Prevention to minimize the potential introducing contaminants including functional closed operation, accepted connecting technology, raw material control and sourcing. Then remove to verify capacity of manufacturing process in bio burden removal such as sanitized resin column and system and also put like 0.22 filters at key positions last detection to verify absence of bare burden. It is best to get the test results on the same day. Then we can take corresponding actions. So we use the rapid bare burden testing method. The integral system from into bio company for our high CB platform FTP was so fast so but the MCC usually needs to run for more than like 15 days. It is the worst case since we are loading growth promoting silk culture media at room temperature. So here I will use MCC as an example to describe our control strategy in practice. The diagram on the left shows the simple process flow path of MCC. For better understanding again first prevention the MCC system, use single use gamma array edited manifolds make the system itself stereo and the accepted connection technology avoid open operation, lower the risk of microbial introduction, then remove. We placed stereo filter at key positions such as the buffer and sample inlet also at the waste outlet for protection. Coupled with the strict sanitization wash with the high concentration of sodium hydroxide, last detection, close the sampling and rapid about a burden test is applied. We set a sampling point at HCCF tank post column protein pool and even at the end of waistline, we have a cycle collection tank before the protein pool so that we can take product diversion according to the bell burden results of the day. All this above play an important role in bell burden control during MCC operation. However, one problem we met in the at scale testing with the cleaning of packed column, the reason is not stereo when it leaves the factory and the column packing cannot be operated completely closed, so the column packing becomes the main risk of contamination. What's more, we faced another challenge is that even treated by high concentration of sodium hydroxide, the bacillus spoil still could not be killed, resulted in rapid contamination of system and product. After in many investigations and attempts, we found some solutions. For reference, first try using more active reagents such as a mixture of benzo alcohol and isopropanol or oxidizing agent prosthetic acid PAA. PAA showed better performance in repeated tests but noted that PA should be prepared and used immediately. Secondly, cleaning procedures can be improved by extending contact time and it is better to pre sanitize the empty column and the resin separately before column packing. All these strategy and the measures have been confirmed for better burden control at a large scale. And after so much discussed, let's take a look at the real GMP implementation of high CB purification platform. This case is a 300 liters profession. It was transferred from batch purification process to high CB hybrid continuous process. The batch process required capture every three days, so six capture lots are needed over 18 days. When using the continuous process, only one startup is required, Then MCC can run automatically for 18 days without additional preparation work. They increase the productive productivity, also decrease the upper front resin from 25 liters to 10 liters. Addition continuous capture also saves six 2000 liters storage bags and reduce the clarify the harvest storage time from 96 hours to less than 24 hours. Then it is followed by depth fluctuation to flow through polishing, chromatography and various fluctuation. These independent process need a different group of professionals to prepare and run in four days. While just one operation on FTP, these four steps can be fully automated in 35 hours. This free up almost 4040% of downstream capacity and reduced the upfront resin from 38 liters to 15 liters. It saved a lot of labour and in processed whole tank. Of course, to ensure the success of GMP production for the first attempt, we do a lot of preparation work and the risk management. After MCC arrived, we complete IOQ and the functional test in the first time. Then we test with cell culture media. However, we mentioned in the first try, we faced by a burden contamination after serious improvement. As I described the last section, we finally control the growth of microbial in the third round. To eliminate the chance and test the robustness of control strategy, we performed another 4 media run and one protein run over the next few months. Similar the FTP system, complete ILQ and functional test after SAT total 7 product and recycle runs are carried out within one year. We did comprehensive FMEA to identify areas of a higher risk for both MCC and FTP, then mitigated that on the all this effort. Finally, the GMP implementation was successfully completed in August. Now let's have a look at the production results. First is the yield. We compared high CB downstream process with three lots of the previous batch process. The figure left show the step yield and the figure right show the overall yield. The high CB process is in highlighted in yellow bar on the right. You can see both step yields and overall yields are very comparable to the previous batch. Then we take a look at the MCC performance. Here is the actual cryptography profile. The dense UV curves on the left show the uninterrupted loading of HCCF during the 18 days run. The three columns complete 106 protea cycles in total. The average yield is about 95% and more than more purity is more than 98% in the illusion pool. The graph on the right compares the UV curve of the 1st and the 34 cycles of single column. The almost the same curve illustrates the good column performance after 18 days and for process quality. Since the exact data is not disclosed yet, what I'd say is that recovery, monomer purity and impurity residues such as HCPDNA and RE reach the protein are expected and very comparable to batch process and while rapid by burden testing. We monitor by burden post column every day and achieve 0 CFU for 18 plus days. The results were formally verified using conventional method confirm that our control strategy is stable and effective. And this page show the process quality attributes of the protein after, before and after FTPFTP complete processing more than 15 kilogram products from the entire profession in 35 hours. To better understand the process performance of the different stage within this 35 hours, samples are taken at the beginning, middle and end of the FTP run. The HCP, SCC purity and a DNA residue shows that FTP based purification provides good impurity removed through the process. PCOA and overall yield it's about 80% are constant compared to the batch process. Say there is no bear burden issue during FTP running and after GMP run, we evaluate and find that there is potential to further increase FTP throughput looking forward to half the cycle time. To sum up, ICB continuous process have successfully implemented in GMP production with similar performance but much higher throughput compared to batch process. Now let me do a quick overall conclusion. Today, we introduce the continuous downstream platform, highlight the process design and consideration for MCC and FTP. Then we discuss the Biburden control strategy and specific procedures developed by HJB for long term continuous operation. Finally, we present our first success in GMP implementation, producing comparable product and yield. They significantly decrease labor and operation risks, reduced in process hold tanks and increase daily output. For future, we will complete a process characterization and prepare for PPQ runs and a commercial launch. And we will collaborate to improve FTP further enhance the throughput and the robustness. That's all I want to share. Thanks and Chris, I will handle it over to you for your comments. Thanks. Yeah, so I, I just want to take this opportunity to really thank the entire team for getting us to this major milestone. Specifically, I want to highlight our HJB team. We are a relatively small company and you know, this amazing team on really help us to, you know, get the job done in a short amount of time while they're still supporting multiple CMC development projects. Specifically I want to highlight Victor who's the project lead for this continuous downstream project. Obviously, Joelle on the PD side, Vincent, our most experienced operator on the manufacturing side, Nora and Simon, Simon's the head of the downstream group as well as the rest of the manufacturing QCQA and all the analytical science teams. Of course, I also want to acknowledge Philip who is the CSO for into bio, who provided this into growth technology that allows us to do fast bio burden detection to help support our bio burden control strategy. And lastly, obviously, I really want to thank the Miliport team that help us to design and deliver this piece of technology even during our COVID. And I know there was, you know, some delays left, which is, you know, perfectly understandable, but it really helped us to meet our timeline. And also I want to thank them for their continuous support. So with that, I think that's I also wanted to carry the cover and I'll turn it back to you guys. Thanks a lot, Chris and Joel for this great presentation. And I would like to thank you for your attention. And if you need to contact us, you have here all the information. So let's move now to the poll questions before moving to the Q&A session. And Veronica, I'm ending it over to you. Thank you. Thank you everybody and. All right, everyone, it's time for the first poll question here on your screen. You should see a question there. What types of processes are you working on for your implementation in the next three years? A intensified unit operations not connected. B intensified with some integrated connected operations. C intensified semi continuous process. B intensified and fully continuous process or eat. We're not working on on intensification or integration in the next three years. We will give you a few moments to answer that. It's let's see, it's time for questions that come in from our audience. I'm going to read a couple that came in. The first one here I see is can the FTP technology work for all therapeutic proteins? Hello. OK. And you're coming? Yeah. Yeah, I can hear. You. OK, let me ask answer this question and we know that many audience may have interest in the STP and curious about it. The STP system we call developed can either be operated in complete flow through mode or or the second policy step operated in a binary mode. So based on our experience, we believe it is flexible enough for most molecules by good process optimization. But likely I know there will be some more complicated molecules where you may need like two bandit loot or three steps of chromatography. In this case the FTP may not applicable and and we will resort to a batch downstream for polishing steps because the MCC is still works and you know, our facilitated design allowed us to do both modes of the purification. And I think this hope this can answer the question. Thank you, Joel. The next question we have here, I also forgot to mention everybody that I can. I wanted to remind you that it's not too late to send us questions using the Q&A widget. And this also applies to any on demand viewers. We'll try to get through all of them, but if we run out of time, we'll respond to you individually. And as a reminder, this webinar will be available on our website soon and all participants will receive an e-mail notification when it's available for viewing. So I forgot to mention that, sorry. And then the next question we have here is, is the FTP technology commercially available and if yes, when? Yes, I can answer that one. So currently the system could be built as a custom product looking at that filtration followed by anionic chains and cationic chains and virus filtration as shown here. We do have plans that we're currently working on to incorporate more features focusing on process flexibility primarily for our standard offering, which would be something that we're looking at being available in 2025. S certainly reach out if you have more questions. Thanks, Kara. Next question is, compared to batch, what are the major differences in process development and characterization for a continuous process? OK, let me answer this one. So I didn't discuss this too much in in my presentation because it is a quite big question out of the platform and due to the different platform, I think every company has their own strategy basing basing on our experience for the development, both batch and continuous downstream aim at the Purify the products to satisfy the quality with a higher yield. So I think the process intensification strategy should be similar. For example, to limit the dilution operations, sharing buffers between different steps and improve the loaded density of each chromatography and the filtration step. The one unique features for continuous is pay more attention to the integration of unit steps and build a robust and automated control strategy including a surge tank design and process flow design just as I described in the presentation. And that's why the flow through process is favored and where a hybrid that continues can ease the development. As for process characterization, it is also similar to do a continuous compared with a batch one and special considerations according to the mmap like variation of proficient period to downstream process and unplanned posing significant difference in the loading density and the robust of inline adjustment. These are all simplified in our hybrid process that is a bigger advantage. But there are do have some points we think are different from a batch. First is I think is the relevant time distribution. The approach is unnecessary to study the product stability for a continuous process. For example, during loading where the loading material is exposed to the resin and when you're posing how long the product stay in the third tank or the columns we need to study and it helps better understanding your process and guiding on the product diversion. Another point I think is the various for various clearance study. Yeah, make sure your model based approach for VC study and represent the feed variation and cover the worst conditions in your continuous process. Yeah. And these are my understanding and I hope this can help you a bit. Yeah. Thank you. Our next question here is if if COGS is so important, why don't you go with large stainless scale? Ronnie, did you say COGS, cost of goods? Yeah, yeah. Oh, OK, OK, OK, yeah, maybe, maybe, maybe I can take that one. So you know, first of all, I guess I would say I don't have hundreds of millions of dollars available to me. And even if I do, I would invest that into drug development clinical study because you know how expensive clinical trials are. But you know the whole point of processing testification like high CB is that it allow a relatively low cost facility to manufacture. I would say. Metric tons of product to support blockbuster product as well as multi products. Just give you an example using 6 by 1000 user perfusion process with a reasonable productivity or let's say 3G per day, we can produce more than three metric tons of product at a cost of goods. I would say much lower than $50 per gram at a facility called. That's I would say 1/4 of what the traditional stainless steel facility would cost with a similar output. Just give you some some context. When we built a facility back in 2018 using this G com prefabricated clean room technology, the cost was around 40 to maybe $43 million at that time. Since then we have chip off capacity and added ADP line using a Bosch isolated technology, I would say for less than $18 million with only one or two months facility shut down. So it could give you an idea the agility of type this type of facility by applying processing this vacation. So certainly stainless steel, a large stainless steel facility give you the economy of scale but and also low cost of goods. But that's only assuming that they're operating at very efficient at full capacity. But you have to remember that for that type of facility typically takes four to five years to get the capacity ready. So when they're designing and constructing the facility, they're not looking at just the first four to five years of demand, they're looking at more like 10 years, which means that the facility can be very big and then the capacity utilization, at least for the first few years is going to be fairly low, which means the cost goes actually be very high. So you know, that's why if you know, we don't do the the stainless steel facilities for the reason that that I just mentioned. And also in terms of demand uncertainties, you know, in my career I have seen facility hundreds of $1,000,000 facility that's been set idle because of clinical failure or you know, over projection of market demand. So you know, so I think that's the reason why, you know, we would not build stainless steel facilities just for the lower cost. We use process intensification to keep the facility cost down and also keep the cost cocks down. So that I think that's why we, you know, we don't do it that way. Hopefully that answers the question. Thank you. OK. And there's another question here. Let's see. Do you have an interest to have a more flexible, modular and interconnected system between each unit operation? Yes, I can take that one. So yes, that, that actually is the intent. I think Chris had a nice word, right? Agility. That's what we want the system to be. So, so the plan is to make it so that everything is connected from bioreactor right through to say bulk drug substance. And so you know, we talked about the four unit operations for flow through polishing here, but the the intent for you know, going into 2025 with a standard option would be to make it indeed modular so that the customer can choose what unit operations they'd like to have in that polishing kind of sub grouping. So hopefully that answers the question. But yes, the short answer is yes, to be more flexible, modular and agile. Thanks, Karen. OK. It looks like we answered everyone's questions. But again, if you have another question, you can still submit it. I'm sorry. I checked. Yeah. There is one question I see here about Bio Burton. No. Oh yeah, yeah, yeah, I think what? Happens. When you detect bio burden in your MCC operation. Do you want? Do you want taking that one? Yeah, Yeah. Let me answer this. That's interesting. And I think the risk is quite low due to so many media and the test runs showing the very low bio burden testing. But in the event if the burden is detected, the system, I mean the MC system during the operation will be put on a post and the the harvest clarified harvest will be collected in the surgery tank continually. But we designed enough buffer space in the surgery vessel and while at the same time the existing single use flow kit we used for MCC and the three columns will be replaced in case with a new set of single use blockade and then three pre sanitized columns. Yes, we prepared ahead of time and once the MCC operation resume, our design space allowed us to increase the processing fluid until the targeted level is in search tank is reached. So it is safe. Then the produced product, the protein pool is also segregated and we'll wait for the final burden and that endotoxin test results by conventional method, we will combine it together if the test, test results is good and also based on the project quality assessment. Otherwise the reporting April will be discussed. That is our brief action strategy and I hope this can answer this question. That's it. Thank you, Joe. So I think that is it. If there's any more, Nope, I think we answered all of them. So thank you everyone for all of the questions. If we didn't get to your question, please feel free to e-mail our presenters directly. And to register for future webinars or to access our archived webinar library, please visit our website. Again, I'd like to thank all of this, all of you, for joining us today and all of our speakers for today's presentation. Have a great day everybody. Thank you. Thank you. Bye. Thank you. _1732499056725

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